Gleason Grade Progression Is Uncommon

Abstract

Gleason grade is universally used for pathologic scoring the differentiation of prostate cancer. However, it is unknown whether prostate tumors arise well-differentiated and then progress to less differentiated forms or if Gleason grade is an early and largely unchanging feature. Prostate Specific Antigen (PSA) screening has reduced the proportion of tumors diagnosed at advanced stage, which allows assessment of this question on a population level. If Gleason grade progresses as stage does, one would expect a similar reduction in high grade tumors. We studied 1,207 Physicians’ Health Study and Health Professionals Follow-up Study participants diagnosed with prostate cancer 1982–2004 and treated with prostatectomy. We compared the distribution of grade and clinical stage across the pre-PSA and PSA screening eras. We re-reviewed grade using the ISUP 2005 revised criteria. The proportion of advanced stage tumors dropped more than six-fold, from the earliest period (12/1982–1/1993), 19.9% stage ≥T3, to the latest (5/2000–12/2004), 3% stage T3, none T4. The proportion of Gleason score ≥8 decreased substantially less, from 25.3% to 17.6%. A significant interaction between stage and diagnosis date predicting grade (p=0.04) suggests the relationship between grade and stage varies by time period. As the dramatic shift in stage since the introduction of PSA screening was accompanied by a more modest shift in Gleason grade, these findings suggest grade may be established early in tumor pathogenesis. This has implications for the understanding of tumor progression and prognosis, and may help patients diagnosed with lower grade disease feel more comfortable choosing active surveillance.

Role of steroid receptor and coregulator mutations in hormone-dependent cancers

“…In 2017, approximately 161,360 men will be diagnosed with PCa in the United States -of whom an estimated 26,730 will die from the disease (2). Nearly all diagnosed cases are localized (3) and are treated by surgery or radiotherapy. While these treatments are initially effective, many patients rapidly relapse and develop recurrent metastatic disease, which is often fatal, as evidenced by a five-year survival rate of 28% (4).…”

“…Role of steroid receptor and coregulator mutations in hormone-dependent cancers Anna C. Groner 1,2,3 and Myles Brown…”

WOMEN IN CANCER THEMATIC REVIEW: Diverse functions of DNA methylation: implications for prostate cancer and beyond

“…Both genetic and demographic factors contribute to the high incidence of prostate cancer (Al Olama et al 2014). Clinically, elevated prostate-specific antigen (PSA) in the blood serves as an early marker for prostate cancer; early detection has led to approximately 90% of prostate cancers still being localized to the prostate at the time of diagnosis (Penney et al 2013). However, disease outcome is highly variable on a spectrum ranging from indolent disease that can be monitored by active surveillance to highly aggressive disease that leads to death.…”

“…A useful predictor of prostate cancer aggressiveness is the Gleason grade (Epstein et al 1996, Albertsen et al 1998, Pan et al 2000, Penney et al 2013. The presence of Gleason pattern 4/5 cancers is associated with increased development of metastatic disease, morbidity and 23:11 mortality compared with Gleason 3 cancers (Stamey et al 1999, Humphrey 2004.…”

Disease-Specific Survival in Prostate Cancer Patients : Results from the Scandinavian Prostate Cancer Group (SPCG) Trial No. 5 and Regional Cancer Register Data

“…Studies with shorter follow-up may overestimate survival prognosis for these men if simple extrapolation is used. There are still insufficient morphologic or molecular biologic explanations for the instability and clinical progress of PCa over time [183][184][185].…”